Abnormal spindle-like, microcephaly associated

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Abnormal spindle-like microcephaly-associated protein , also called abnormal spindle protein homolog or asp homolog for short, ASPM for short, is a protein thatis encoded in humans by the gene for ASPM. This ASPM geneis located on chromosome 1 ( gene locus 1q31; MCPH5). Defective forms of the gene are likely one of the possible causes of the autosomal recessive form of primary microcephaly .

ASPM is the short name of the protein, which is an acronym for English. " A BNORMAL sp indle-like, m icrocephaly-associated " refers to the orthologous protein Asp ( " Abnormal spindle ") in Drosophila melanogaster . This 1954 amino acid long "protein abnormal spindle" as a product of the asp gene of the fruit fly contains 5 binding domains with IQ motifs for calmodulin and is, among other things, important for a normally functioning mitotic spindle apparatus in embryonic neuroblasts.

The mouse gene Aspm is expressed prenatally in the cortex cerebri during neurogenesis and codes for the homologous protein ASPM (3122 AS , 32 IQ domains). The main difference between the genes Aspm in mice and ASPM in humans is a single, large insertion which codes for repetitive IQ motifs in the human protein ASPM (3477 AS, 39 IQ domains). Studies in mice show that the Aspm gene product is also involved in spindle regulation here. This function is apparently evolutionarily conserved, for that from the nematode Caenorhabditis elegans gene ASPM-1 protein expressed ASPM-1 (1186 AS, with 2 IQ domains) could also be localized at spindle fibers, where in the meiotic nuclear division, the rotation of the nuclear mitotic spindle and in the mitotic the organization and position of the spindle poles through interactions with calmodulin and dynein as well as LIN-5 .

evolution

In humans, a new allele of ASPM appeared about 14100 to 500 years ago (estimated mean about 5800 years). The new allele today has a gene frequency of around 50% in the Middle East and Europe, it is found less often in East Asia and only a little in Sub-Saharan Africa. It is also found in great penetration among the people of Papua New Guinea , with a frequency of 59.4%.

The occurrence of the new ASPM allele, roughly estimated using the statistical mean of 5800 years, would thus roughly coincide with the cultural development of agriculture, cities and writing. There are currently two alleles of this gene: the older (about 5800 years old) and the newer (about less than 5800 years old). About 10% of all people have two copies of the new allele, while about 50% have two copies of the old allele. The remainder of 40% of all people have one of the two. Half of the 50% with at least one new allele have an identical copy of the new allele. This indicates a rapid spread of the original mutant of ASPM . According to the "selective sweep" hypothesis, a mutation that spreads rapidly speaks for a beneficial way for the affected individual, which is associated with it in some way.

If you test the IQ of those with the new or old ASPM allele, you won't find any differences, so that the assumption that this gene would influence intelligence is not tenable. On the other hand, statistical studies show that the older form of the gene is found more than average in populations that speak tonal languages such as Chinese or African languages ​​of the Sahara. However, the gene for ASPM is not only expressed in neuronal progenitor cells during embryonic neurogenesis, but also, for example, during spermatogenesis or oogenesis in cells of the germ line , for example in mice.

Web links

Individual evidence

  1. ↑ a b Lisa Pattison, Yanick J. Crow, V. Jayne Deeble, Andrew P. Jackson, Hussain Jafri, Yasmin Rashid, Emma Roberts, C. Geoffrey Woods: A fifth locus for autosomal recessive primary microcephaly maps to chromosome 1q31 . In: Am. J. Hum. Genet. . 67, No. 6, December 2000, pp. 1578-1580. doi : 10.1086 / 316910 . PMID 11078481 . PMC 1287934 (free full text).
  2. ↑ The names, short names and symbols of genes are - if it is necessary, as in this context, to distinguish between gene and gene product - following the usual conventions in italics , those of proteins are not.
  3. ↑ a b Jacquelyn Bond, Emma Roberts, Ganesh H. Mochida, Daniel J. Hampshire, Sheila Scott, Jonathan M. Askham, Kelly Springell, Meera Mahadevan, Yanick J. Crow, Alexander F. Markham, Christopher A. Walsh, C. Geoffrey Woods: ASPM is a major determinant of cerebral cortical size . In: Nat. Genet. . 32, No. 2, October 2002, pp. 316-20. doi : 10.1038 / ng995 . PMID 12355089 .
  4. ↑ see entry UniProtKB - Q8CJ27 (ASPM_MOUSE) in the bioinformatic database for proteins UniProt .
  5. ↑ M. Bähler, A. Rhoads: Calmodulin signaling via the IQ motif . In: FEBS Lett. . 513, No. 1, February 2002, pp. 107-113. doi : 10.1016 / S0014-5793 (01) 03239-2 . PMID 11911888 .
  6. ↑ JL Fish, Y. Kosodo, W. Enard, S. Pääbo, WB Huttner: ASPM specifically Maintains symmetric proliferative divisions of neuroepithelial cells . In: Proc. Natl. Acad. Sci. USA . 103, No. 27, July 2006, pp. 10438-10443. bibcode : 2006PNAS..10310438F . doi : 10.1073 / pnas.0604066103 . PMID 16798874 . PMC 1502476 (free full text).
  7. ↑ Monique van der Voet, Christian WH Berends, Audrey Perreault, Tu Nguyen-Ngoc, Pierre Gönczy, Marc Vidal, Mike Boxem, Sander van den Heuvel: NuMA-related LIN-5, ASPM-1, calmodulin and dynein promote meiotic spindle rotation independently of cortical LIN-5 / GPR / Gα . In: Nature Cell Biology . 11, No. 3, 2009, ISSN  1465-7392 , pp. 269-277. doi : 10.1038 / ncb1834 .
  8. ↑ a b Patrick D. Evans, Sandra L. Gilbert, Nitzan Mekel-Bobrov, Eric J. Vallender, Jeffrey R. Anderson, Leila M. Vaez-Azizi, Sarah A. Tishkoff, Richard R. Hudson, Bruce T. Lahn: Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans . In: Science . 309, No. 5741, September 2005, p. 1717. bibcode : 2005Sci ... 309.1717E . doi : 10.1126 / science.1113722 . PMID 16151009 .
  9. ↑ a b Nitzan Mekel-Bobrov, Sandra L. Gilbert, Patrick D. Evans, Eric J. Vallender, Jeffrey R. Anderson, Richard R. Hudson, Sarah A. Tishkoff, Bruce T. Lahn: Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens . In: Science . 309, No. 5741, September 2005, pp. 1720-1722. bibcode : 2005Sci ... 309.1720M . doi : 10.1126 / science.1116815 . PMID 16151010 .
  10. ↑ What Makes Us Human? Discovery Channel / Channel 4 , 2006 (documentary series).
  11. ↑ Mason Inman: Human brains enjoy ongoing evolution. In: newscientist.com. New Scientist, accessed February 20, 2016 .
  12. ^ A b Mathias Currat, Laurent Excoffier, Wayne Maddison, Sarah P. Otto, Nicolas Ray, Michael C. Whitlock, Sam Yeaman: Comment on "Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens" and "Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans " . In: Science . 313, No. 5784, July 2006, p. 172; author reply 172. doi : 10.1126 / science.1122712 . PMID 16840683 .
  13. ↑ Roger P. Woods, Nelson B. Freimer, Joseph A. De Young, Scott C. Fears, Nancy L. Sicotte, Susan K. Service, Daniel J. Valentino, Arthur W. Toga, John C. Mazziotta: Normal variants of Microcephalin and ASPM do not account for brain size variability . In: Hum. Mol. Genet. . 15, No. 12, June 2006, pp. 2025-2029. doi : 10.1093 / hmg / ddl126 . PMID 16687438 .
  14. ↑ Nitzan Mekel-Bobrov, Danielle Posthuma, Sandra L. Gilbert, Penelope Lind, M. Florencia Gosso, Michelle Luciano, Sarah E. Harris, Timothy C. Batesm Tinca JC Polderman, Lawrence J. Whalley, Helen Fox, John M. Starr , Patrick D. Evans, Grant W. Montgomery, Croydon Fernandes, Peter Heutink, Nicholas G. Martin, Dorret I. Boomsma, Ian J. Deary, Margaret J. Wright, Eco JC de Geus, Bruce T. Lahn: The ongoing adaptive evolution of ASPM and Microcephalin is not explained by increased intelligence . In: Hum. Mol. Genet. . 16, No. 6, March 2007, pp. 600-608. doi : 10.1093 / hmg / ddl487 . PMID 17220170 .
  15. ^ Dan Dediu, D. Robert Ladd: Linguistic tone is related to the population frequency of the adaptive haplogroups of two brain size genes, ASPM and Microcephalin . In: Proc. Natl. Acad. Sci. USA . 104, No. 26, June 2007, pp. 10944-10949. bibcode : 2007PNAS..10410944D . doi : 10.1073 / pnas.0610848104 . PMID 17537923 . PMC 1904158 (free full text).
  16. ↑ Jeremy N. Pulvers, Jarosław Bryk, Jennifer L. Fish, Michaela Wilsch-Bräuninger, Yoko Arai, Dora Schreier, Ronald Naumann, Jussi Helppi, Bianca Habermann, Johannes Vogt, Robert Nitsch, Attila Tóth, Wolfgang Enard, Svante Pääbo, Wieland B. Huttnera: Mutations in mouse Aspm (abnormal spindle-like microcephaly associated) cause not only microcephaly but also major defects in the germline . In: Proc Natl Acad Sci (PNAS) . 107, No. 38, September 2010, pp. 16595-16600. doi : 10.1073 / pnas.1010494107 . PMC 2944708 (free full text).